MARTIN’S PHYSICAL PHARMACY AND PHARMACEUTICAL …

1 P1:Trim: 30, 200922:0iMARTIN S PHYSICAL PHARMACYAND PHARMACEUTICAL SCIENCESP hysical Chemical and Biopharmaceutical Principlesin the PHARMACEUTICAL SciencesSIXTH EDITIONE ditorPATRICK J. SINKO, PhD, RPhProfessor II (Distinguished)Parke-Davis Chair Professor in Pharmaceutics and Drug DeliveryErnest Mario School of PharmacyRutgers, The State University of New JerseyPiscataway, New JerseyAssistant EditorYASHVEER SINGH, PhDAssistant Research ProfessorDepartment of PharmaceuticsErnest Mario School of PharmacyRutgers, The State University of New JerseyPiscataway, New JerseyP1:Trim: 30, 200922:0 Editor:David B. TroyProduct Manager:Meredith L. BrittainVendor Manager:Kevin JohnsonDesigner:Holly McLaughlinCompositor:Aptara , EditionCopyrightc 2011, 2006 Lippincott Williams & Wilkins, a Wolters Kluwer West Camden StreetBaltimore, MD 21201530 Walnut , PA 19106 Printed in ChinaAll rights reserved.

2 This book is protected by copyright. No part of this book may be reproducedor transmitted in any form or by any means, including photocopies or scanned-in or other electroniccopies, or utilized by any information storage and retrieval system without written permission fromthe copyright owner, except for brief quotations embodied in critical articles and reviews. Materialsappearing in this book prepared by individuals as part of their official duties as governmentemployees are not covered by the above-mentioned copyright. To request permission, please contactLippincott Williams & Wilkins at 530 Walnut Street, Philadelphia, PA 19106, via e-mail at or via Website at (products and services).987654321 Library of Congress Cataloging-in-Publication DataMartin s PHYSICAL PHARMACY and PHARMACEUTICAL sciences : physicalchemical and biopharmaceutical principles in the pharmaceuticalsciences. 6th ed.

3 / editor, Patrick J. Sinko ; assistant editor,Yashveer ; bibliographical references and 978-0-7817-9766-51. PHARMACEUTICAL chemistry. 2. Chemistry, PHYSICAL and Martin, Alfred N. II. Sinko, Patrick J. III. Singh, Title: PHYSICAL PHARMACY and PHARMACEUTICAL sciences.[DNLM: 1. Chemistry, PHARMACEUTICAL . 2. Chemistry, PHYSICAL . QV 744M386 2011] 2011615 .19 dc222009046514 DISCLAIMERCare has been taken to confirm the accuracy of the information present and to describe generallyaccepted practices. However, the authors, editors, and publisher are not responsible for errors oromissions or for any consequences from application of the information in this book and make nowarranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contentsof the publication. Application of this information in a particular situation remains the professionalresponsibility of the practitioner; the clinical treatments described and recommended may not beconsidered absolute and universal authors, editors, and publisher have exerted every effort to ensure that drug selection anddosage set forth in this text are in accordance with the current recommendations and practice at thetime of publication.

4 However, in view of ongoing research, changes in government regulations, and theconstant flow of information relating to drug therapy and drug reactions, the reader is urged to checkthe package insert for each drug for any change in indications and dosage and for added warningsand precautions. This is particularly important when the recommended agent is a new or infrequentlyemployed drugs and medical devices presented in this publication have Food and Drug Administration(FDA) clearance for limited use in restricted research settings. It is the responsibility of the healthcare providers to ascertain the FDA status of each drug or device planned for use in their purchase additional copies of this book, call our customer service department at (800) 638-3030or fax orders to (301) 223-2320. International customers should call (301) Lippincott Williams & Wilkins on the Internet: at Lippincott Williams &Wilkins customer service representatives are available from 8:30 am to 6:00 pm, :Trim: 30, 200922:0 Dedicated to my parents Patricia and Patrick Sinko,my wife Renee, and my children Pat, Katie (and Maggie)iiiP1:Trim: 30, 200922:0 DEDICATIONALFRED N.

5 MARTIN (1919 2003)This fiftieth anniversary edition ofMartin s PHYSICAL Phar-macy and PHARMACEUTICAL Sciencesis dedicated to the mem-ory of Professor Alfred N. Martin, whose vision, creativity,dedication, and untiring effort and attention to detail led tothe publication of the first edition in 1960. Because of hisnational reputation as a leader and pioneer in the then emerg-ing specialty of PHYSICAL PHARMACY , I made the decision tojoin Professor Martin s group of graduate students at Pur-due University in 1960 and had the opportunity to witnessthe excitement and the many accolades of colleagues fromfar and near that accompanied the publication of the firstedition ofPhysical PHARMACY . The completion of that workrepresented the culmination of countless hours of painstak-ing study, research, documentation, and revision on the partof Dr. Martin, many of his graduate students, and his wife,Mary, who typed the original manuscript.

6 It also representedthe fruition of Professor Martin s dream of a textbook thatwould revolutionize PHARMACEUTICAL education and Pharmacywas for Professor Martin truly a labor oflove, and it remained so throughout his lifetime, as he workedunceasingly and with steadfast dedication on the subsequentrevisions of the publication of the first edition ofPhysical Pharmacygenerated broad excitement throughout the national and inter-national academic and industrial research communities inpharmacy and the PHARMACEUTICAL sciences. It was the world sfirst textbook in the emerging discipline of PHYSICAL pharmacyand has remained the gold standard textbook on the appli-cation of PHYSICAL chemical principles in PHARMACY and thepharmaceutical PHARMACY , upon its publi-cation in 1960, provided great clarity and definition to a dis-cipline that had been widely discussed throughout the 1950sbut not fully understood or adopted.

7 Alfred Martin sPhysi-cal Pharmacyhad a profound effect in shaping the directionof research and education throughout the world of pharma-ceutical education and research in the PHARMACEUTICAL indus-try and academia. The publication of this book transformedpharmacy and PHARMACEUTICAL research from an essentiallyempirical mix of art and descriptive science to a quantita-tive application of fundamental PHYSICAL and chemical scien-tific principles to PHARMACEUTICAL systems and dosage Pharmacyliterally changed the direction, scope,focus, and philosophy of PHARMACEUTICAL education during the1960s and the 1970s and paved the way for the specialty dis-ciplines of biopharmaceutics and pharmacokinetics which,along with PHYSICAL PHARMACY , were necessary underpinningsof a scientifically based clinical emphasis in the teaching ofpharmacy students, which is now pervasive throughout phar-maceutical the time of the initial publication ofPhysical Phar-macyto the present.

8 This pivotal and classic book has beenwidely used both as a teaching textbook and as an indis-pensible reference for academic and industrial researchers inthe PHARMACEUTICAL sciences throughout the world. This sixthedition ofMartin s PHYSICAL PHARMACY and PharmaceuticalSciencesserves as a most fitting tribute to the extraordinary,heroic, and inspired vision and dedication of Professor Mar-tin. That this book continues to be a valuable and widelyused textbook in schools and colleges of PHARMACY through-out the world, and a valuable reference to pharmaceuticalscientists and researchers, is a most appropriate recognitionof the life s work of Alfred Martin. All who have contributedto the thorough revision that has resulted in the publicationof the current edition have retained the original format andfundamental organization of basic principles and topics thatwere the hallmarks of Professor Martin s classic first editionof this seminal Martin always demanded the best of himself, hisstudents, and his colleagues.

9 The fact that the subsequent andcurrent editions ofMartin s PHYSICAL PHARMACY and Phar-maceutical Scienceshave remained faithful to his vision ofscientific excellence as applied to understanding and apply-ing the principles underlying the PHARMACEUTICAL sciences isindeed a most appropriate tribute to Professor Martin s mem-ory. It is in that spirit that this fiftieth anniversary edition isformally dedicated to the memory of that visionary and cre-ative pioneer in the discipline of PHYSICAL PHARMACY , AlfredN. L. Colaizzi, PhDRutgers, The State University of New JerseyPiscataway, New JerseyNovember 2009ivP1:Trim: 30, 200922:0 PREFACEEver since the First Edition ofMartin s PHYSICAL Pharmacywas published in 1960, Dr. Alfred Martin s vision was to pro-vide a text that introduced PHARMACY students to the applica-tion of PHYSICAL chemical principles to the PHARMACEUTICAL sci-ences. This remains a primary objective of the Sixth s PHYSICAL Pharmacyhas been used by generations ofpharmacy and PHARMACEUTICAL science graduate students for50 years and, while some topics change from time to time,the basic principles remain constant, and it is my hope thateach edition reflects the PHARMACEUTICAL sciences at that pointin with prior editions, this edition represents an updating ofmost chapters, a significant expansion of others, and the addi-tion of new chapters in order to reflect the applications of thephysical chemical principles that are important to the Phar-maceutical Sciences today.

10 As was true when Dr. Martin wasat the helm, this edition is a work in progress that reflectsthe many suggestions made by students and colleagues inacademia and industry. There are 23 chapters in the SixthEdition, as compared with 22 in the Fifth Edition. All chap-ters have been reformatted and updated in order to makethe material more accessible to students. Efforts were madeto shorten chapters in order to focus on the most importantsubjects taught in PHARMACY education today. Care has beentaken to present the information in layers from the basicto more in-depth discussions of topics. This approach allowsthe instructor to customize their course needs and focus theircourse and the students attention on the appropriate topicsand the publication of the Sixth Edition, a Web-basedresource is also available for students and faculty members(see the Additional Resources section later in this preface).